Methods and compositions relating to the treatment of tumors

Abstract

Described herein are methods and compositions relating to the treatment of a tumor (e.g., schwannoma) by increasing expression of Apoptosis-associated Speck-like protein containing a CARD (ASC) and/or gasdermin D. In some embodiment, the increased expression is provided by means of a vector or construct comprising a nucleic acid encoding Apoptosis-associated Speck-like protein containing a CARD (ASC) and/or gasdermin D operably linked to a Schwann-lineage cell-specific promoter. In some embodiments, the vector is a viral vector.

What is claimed herein is: 
     
       1. A method of treating a schwannoma in a subject in need thereof, the method comprising:
 administering a viral vector comprising a nucleic acid encoding Apoptosis-associated Speck-like protein containing a CARD (ASC) operably linked to a Schwann cell-specific promoter; and 
 wherein the subject is not administered a viral vector comprising a caspase gene. 
 
     
     
       2. The method of  claim 1 , wherein the ASC is a human, mouse, or rat ASC. 
     
     
       3. The method of  claim 1 , wherein the Schwann cell-specific promoter is a myelin basic protein (P0), a peripheral myelin protein 22 (PMP22), or a myelin basic protein (MBP) promoter. 
     
     
       4. The method of  claim 1 , wherein the promoter is a human or murine promoter. 
     
     
       5. The method of  claim 1 , wherein the subject in need of treatment for a schwannoma is a subject having or diagnosed as having a condition selected from the group consisting of: neurofibromatosis 1 (NF1); neurofibromatosis 2 (NF2); schwannomatosis; meningioma; nerve sheath tumor; schwannoma; vestibular schwannoma; sporadic schwannoma; neurofibrosarcoma; neurofibroma; neurofibromatosis (NF); malignant peripheral nerve sheath tumor; and a combination thereof. 
     
     
       6. The method of  claim 1 , wherein the viral vector is a recombinant adeno-associated virus (rAAV). 
     
     
       7. The method of  claim 6 , wherein the rAAV is of serotype AAV1 or AAV9. 
     
     
       8. The method of  claim 1 , wherein the vector further comprises a polyadenylation signal. 
     
     
       9. The method of  claim 8 , wherein the polyadenylation signal comprises a bovine growth hormone polyadenylation signal (BGHpA), a SV40 polyadenylation signal or a rabbit beta-globin polyadenylation signal. 
     
     
       10. The method of  claim 8 , wherein the vector further comprises a first AAV inverted terminal repeat (ITR) located upstream of the Schwann cell specific promoter and a second AAV ITR located downstream of the polyadenylation signal. 
     
     
       11. The method of  claim 10 , wherein the first or second AAV inverted terminal repeat comprises a deletion of a terminal resolution site. 
     
     
       12. The method of  claim 1 , wherein the vector is a polynucleotide. 
     
     
       13. The method of  claim 1 , wherein the vector is a single-stranded or double-stranded AAV. 
     
     
       14. The method of  claim 1 , wherein the vector is a self-complementary AAV (scAAV). 
     
     
       15. The method of  claim 1 , wherein the vector is a virus particle. 
     
     
       16. The method of  claim 1 , wherein the vector is administered directly to a nerve affected by the schwannoma. 
     
     
       17. The method of  claim 1 , wherein administering is intranervously, intracranially, intratumorally, intramuscularly, intravenously, intradermally, or subcutaneously, or a combination thereof. 
     
     
       18. The method of  claim 1 , wherein the subject is also treated by surgical removal or reduction of the schwannoma. 
     
     
       19. The method of  claim 1 , wherein the subject in need of treatment for a schwannoma is a subject having or diagnosed as having a condition selected from the group consisting of: neurofibromatosis 1 (NF1); neurofibromatosis 2 (NF2); schwannomatosis; meningioma; nerve sheath tumor; schwannoma; vestibular schwannoma; sporadic schwannoma; neurofibrosarcoma; neurofibroma; neurofibromatosis (NF); and a combination thereof. 
     
     
       20. The method of  claim 1 , wherein the subject is also treated by surgical removal of the schwannoma. 
     
     
       21. The method of  claim 1 , wherein the schwannoma is benign.